EP2747573B1 - Zusammensetzungen zur kollagen- und elastinstimulierung sowie ihre verwendung - Google Patents

Zusammensetzungen zur kollagen- und elastinstimulierung sowie ihre verwendung Download PDF

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Publication number
EP2747573B1
EP2747573B1 EP12825830.8A EP12825830A EP2747573B1 EP 2747573 B1 EP2747573 B1 EP 2747573B1 EP 12825830 A EP12825830 A EP 12825830A EP 2747573 B1 EP2747573 B1 EP 2747573B1
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EP
European Patent Office
Prior art keywords
skin
improvement
appearance
aesthetic
reduction
Prior art date
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Not-in-force
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EP12825830.8A
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English (en)
French (fr)
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EP2747573A4 (de
EP2747573A1 (de
Inventor
Daniel Thorn Leeson
Uma Santhanam
John W. Lyga
Siming W. Chen
Russell Wyborski
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Avon Products Inc
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Avon Products Inc
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Publication of EP2747573B1 publication Critical patent/EP2747573B1/de
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates generally to methods for improving the aesthetic appearance and health of human skin.
  • the invention relates to methods and compositions for increasing the production of collagen and elastin in the skin.
  • Unwanted signs include lines and wrinkles, skin sagging or atrophy, loss of suppleness, thickness, plumpness, tautness, elasticity, resiliency, and firmness, and there remains a need for products that combat such signs of aging and, more generally, that provide anti-aging and/or anti-wrinkle effects.
  • the present invention identifies new cosmetic benefits of the botanical extracts Justicia ventricosa, Archidendron clypearia.
  • the invention provides methods for improving the aesthetic appearance of human skin comprising topically applying to an area of the skin in need thereof an effective amount of a botanical extract in a topically acceptable vehicle, wherein said botanical extract is selected from the group consisting of Justicia ventricosa, Archidendron clypearia, and combinations thereof.
  • the said extract is preferably present in an amount effective to up-regulate collagen and/or elastin mRNA expression in human skin fibroblasts. It is believed that up-regulators of collagen and/or elastin mRNA produced within human fibroblasts will lead to increased protein production within the cells, including the fibroblast specific proteins collagen and elastin. Given the importance of fibroblast-produced proteins to overall skin strength and health, upregulation of collagen and/or elastin mRNA is expected to have a beneficial effect on reducing the appearance of aging on skin.
  • the disclosure provides cosmetic compositions comprising a botanical extract of Justicia ventricosa, or combinations thereof, with a topically acceptable vehicle.
  • cosmetic compositions comprising a botanical extract of Archidendron clypearia, and a topically acceptable vehicle, in combination with one or more skin active agents selected from the group consisting of retinoids, anti-oxidants, ⁇ -hydroxy acids, glycolic acid, and thiodipropionic acid and esters thereof.
  • compositions provided herein typically will be formulated in a cosmetically acceptable vehicle and topically applied to a human integument, such as the skin of the face, neck, hands, chest, legs, etc., hair, or nails, for a time sufficient to enhance the health or aesthetic appearance thereof.
  • the botanical extracts are selected from the group consisting of Justicia ventricosa, Archidendron clypearia, and combinations thereof, and may be used as active agents in cosmetic preparation and may be formulated with other cosmetically acceptable components, such as a vehicle, into a composition for topical application to the skin.
  • the compositions are topically applied to the skin in effective amounts, by which is meant an amount sufficient to achieve a measurable improvement in skin health or reduction in one or more dermatological signs of aging.
  • the improvements in the signs of skin aging may generally relate to improvement in the production of elastin and/or collagen, and include without limitation, the following:
  • the aesthetic improvement is treatment, reduction, and/or prevention of fine lines or wrinkles.
  • the said aesthetic improvement of said skin is improvement in thickness, plumpness, and/or tautness.
  • the said aesthetic improvement of said skin is increase in skin elasticity and/or resiliency.
  • the said aesthetic improvement of said skin is treatment, reduction, and/or prevention of skin sagging.
  • the said aesthetic improvement of said skin is improvement in skin firmness.
  • compositions of the invention are applied to skin in need of treatment. That is, skin which suffers from a deficiency or loss in any of the foregoing attributes or which would otherwise benefit from improvement in any of the foregoing skin attributes.
  • the skin is typically treated once or twice daily. The treatment may continue for a week, two weeks, four weeks, eight weeks, six months or longer.
  • the active agents are topically applied, in a cosmetically acceptable vehicle, to skin suffering from fine lines and/or wrinkles to prevent, treat, and/or amelioration the appearance of the fine lines and/or wrinkles in the skin.
  • the compositions are applied to skin in need of treatment, by which is meant skin already having wrinkles and/or fine lines or skin that is at risk of developing fine lines and/or wrinkles.
  • the compositions are applied directly to the fine lines and/or wrinkles on the skin of the face, neck, chest, and/or hands.
  • the invention is directed to a method of improving the aesthetic appearance of skin by increasing the production of collagen and/or elastin in the skin, the method comprising topically applying to an area of the skin in need thereof an effective amount of an agent that up-regulates collagen and/or elastin mRNA expression.
  • agent that up-regulates collagen and elastin mRNA encompasses botanical extracts of Justicia ventricosa, Archidendron clypearia, and combinations thereof. These agents up-regulate the cellular levels of collagen and elastin mRNA, by which is meant that the cellular levels of collagen and elastin proteins are increased by the active agent.
  • up-regulate refers to up-regulation, induction, stimulation, and/or potentiation.
  • the active agents may be, without limitation, activators or agonists, which are compounds that, for example, bind to, stimulate, increase, open, activate, facilitate, enhance activation, sensitize, or up-regulate expression levels of genes or collagen or elastin proteins or peptides.
  • activators or agonists which are compounds that, for example, bind to, stimulate, increase, open, activate, facilitate, enhance activation, sensitize, or up-regulate expression levels of genes or collagen or elastin proteins or peptides.
  • the mechanism by which the collagen or elastin protein are increased is not important.
  • the term “expression levels” refers to an amount of a gene and/or protein that is expressed in a cell.
  • a “gene” includes a polynucleotide containing at least one open reading frame that is capable of encoding a particular polypeptide.
  • polynucleotide is synonymous with “oligonucleotide” and includes polymeric forms of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof, including, without limitation, mRNA, DNA, cDNA, primers, probes, and the like.
  • the preferred methods for measuring expression levels of mRNA encoding collagen and/or elastin involve the quantitation of mRNA expression.
  • Suitable methods for determining mRNA expression include quantitative PCR (QPCR), real-time QPCR, reverse transcription PCR (RT-PCR), and quantitative reverse transcription PCR (QRT-PCR), as are well-known in the art. As described in detail in U.S. Patent Nos.
  • a quantitative reverse transcriptase polymerase chain reaction for detecting mRNA may include the steps of: (a) incubating an RNA sample from the cellular lysate with a reverse transcriptase and a high concentration of a target sequence-specific reverse transcriptase primer under conditions suitable to generate cDNA; (b) subsequently adding suitable polymerase chain reaction (PCR) reagents to the reverse transcriptase reaction, including a high concentration of a PCR primer set specific to the cDNA and a thermostable DNA polymerase to the reverse transcriptase reaction; and (c) cycling the PCR reaction for a desired number of cycles and under suitable conditions to generate PCR products ("amplicons”) specific to the cDNA.
  • PCR polymerase chain reaction
  • the products of the QRT-PCR process may be compared after a fixed number of PCR cycles to determine the relative quantity of the RNA species as compared to a given reporter gene, for example, by Southern blotting. More typically, the progress of the PCR reaction is monitored by analyzing the relative rates of amplicon production for each PCR primer set, for example, by (1) non-specific fluorescent dyes that intercalate with any double-stranded DNA, and/or (2) sequence-specific DNA probes consisting of oligonucleotides that are labeled with a fluorescent reporter which permits detection only after hybridization of the probe with its complementary DNA target.
  • the mRNA may be any mRNA that is associated with collagen and/or elastin proteins, including the mRNAs encoding the subunits identified in Table 1 (COL1A1 and ELN). In a preferred embodiment, the mRNA encodes human COL1A1 and ELN.
  • the plant materials and botanical extracts which up-regulate collagen and elastin mRNA expression may be made of extracts from the following species Justicia ventricosa, Archidendron clypearia, or combinations thereof,
  • Justicia ventricosa is a species of the acanthaceae family, native to China, Burma (Myanmar), India, and Pakistan. It has medium-sized leaves and it produces small white flowers with red spots. It has been used in traditional Chinese medicine, and it is believed to invigorate the circulation of blood, remove hemorrhage, congestion, thrombosis, and local ischemia (microclots) and tissue changes, alleviate lower back pain and pain in lower extremities, traumatic injury, sprain, and arthritis.
  • Archidendron clypearia is a small evergreen tree, in the fabaceae family. It typically has small leaves and produces small while-yellow flowers and orange-red fruits coiled with black seeds. Its leaves have been used for tanning and coloring rattan. It is found in India, Burma (Myanmar), southern China, Malaysia, Thailand, Sri Lanka, Laos, and also in Borneo. It is also known as Inga clypearia, Jack Pithecellobium subcoriaceum, and in Tamil as Malai-vagai, Mazhavagai. In Borneo it is called Anup-anup, J mecanic, Kangkat rangkat, Kelayung, Petai kerayung, and Tambilit.
  • the plant materials may be in any form including, but not limited to, the whole plant, a dried plant, a ground plant, or parts thereof, including but not limited to, seeds, needles, leaves, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, flowers, and meristems, or components and/or constituents found in, or isolated from, the natural plant material, and/or portions of the plant, or any combinations thereof
  • the natural plant material is in the form of an extract derived from the whole plant or from a select portion of the plant, such as the leaves of the plant. It is to be understood that "natural plant material” also includes an ingredient, component, constituent, or extract derived from the natural plant material.
  • the plant extract as used herein also includes "synthetic" extracts, i.e., various combinations of known plant components and/or constituents that are combined to substantially mimic the composition and/or activity of a plant extract of natural origin.
  • synthetic extracts are included in the term "plant extract.”
  • the synthetic extracts will have two or more, three or more, or four or more active ingredients in common with a plant. Most preferably, the synthetic extracts will have substantially the same number of active ingredients as a natural extract.
  • the correspondence of the numerical incidence of active ingredients between the synthetic extracts and the plant or a natural extract may also be described in terms of "percent commonality.”
  • the synthetic extract has about 50 percent or more commonality to the chemical composition of a plant or natural extract.
  • the synthetic extract has about 50 percent or more of the active ingredients found in the plant or a natural extract. More preferably, the chemical composition of the synthetic extract has about 70 percent or more commonality to the chemical composition of a plant or a natural extract. Optimally, a synthetic extract has about 90 percent or more commonality to the chemical composition of a plant or a natural extract.
  • the composition comprises from about 0.0001% to about 90% by weight of a botanical extract of Archidendron clypearia, and a topically acceptable vehicle, in combination with one or more skin active agents selected from the group consisting of retinoids, anti-oxidants, ⁇ -hydroxy acids, glycolic acid, and thiodipropionic acid and esters thereof.
  • the plant extract or components and/or active constituents are preferably derived directly from the plant.
  • the components may be in a pure form, a semi-pure form, or unpurified form.
  • the components are in the form of an extract obtained by aqueous or organic solvent extraction.
  • organic solvents include acetic acid, diethyl ether, ethyl acetate, lower alcohols (e.g., methanol, ethanol, isopropanol, butanol), dichloromethane, chloroform, hexane, benzene, toluene, xylene, petroleum ether, and combinations thereof.
  • the solvent may be either polar or non-polar, protic or aprotic, water-miscible or water-immiscible.
  • the pH may be acidic, neutral, or alkaline.
  • Well-known methods in the art may be used for aqueous or organic solvent extraction. An extraction time between about 1-8 hours at a temperature between about 30°C to about 90 °C is typically suitable.
  • the collected extract is then fine-filtered to remove debris, and may be used directly, or is concentrated, for example by distilling the solvent or by other conventional processing, and the extract can also be provided in powder form.
  • compositions according to the disclosure can be formulated in a variety of forms for topical application and will comprise from about 0.0001% to about 90% by weight of the botanical extract, and preferably will comprise such actives in an amount from about 0.001% to about 25% by weight, and more preferably from about 0.01% to about 1%, 5%, or about 10% by weight. Combinations of botanical extracts are also contemplated. In another embodiment, the composition comprises a combination of two or more substances.
  • compositions can include a cosmetically acceptable vehicle.
  • vehicles may take the form of any known in the art suitable for application to skin and may include, but are not limited to, water; vegetable oils; mineral oils; esters such as octal palmitate, isopropyl myristate and isopropyl palmitate; ethers such as dicapryl ether and dimethyl isosorbide; alcohols such as ethanol and isopropanol; fatty alcohols such as cetyl alcohol, cetearyl alcohol, stearyl alcohol and biphenyl alcohol; isoparaffins such as isooctane, isododecane and is hexadecane; silicone oils such as cyclomethicone, hydrocarbon oils such as mineral oil, petrolatum, isoeicosane and polyisobutene; polyols such as propylene glycol, glycerin, butylene glycol, pentylene glycol and hexylene glycol; liposomes; waxes
  • the vehicle may comprise an aqueous phase, an oil phase, an alcohol, a silicone phase or mixtures thereof and may be in the form of an emulsion.
  • suitable emulsions include water-in-oil emulsions, oil-in-water emulsions, silicone-in-water emulsions, water-in-silicone emulsions, glycerin-in-oil emulsions, wax-in-water emulsions, water-oil-water triple emulsions or the like.
  • the emulsion may include an emulsifier, such as a nonionic, anionic or amphoteric surfactant, or a gelling agent.
  • the topical composition will typically have a pH range from 1 to 8, with a pH in the range of from 2 to 7 being preferred. In some embodiment, the composition will have a pH in the range of from 3.5 to 5.5. Suitable pH adjusters such as citric acid and triethanolamine may be added to bring the pH within the desired range.
  • compositions may include additional skin actives, including but not limited to, botanicals, keratolytic agents, desquamating agents, keratinocyte proliferation enhancers, collagenase inhibitors, elastase inhibitors, depigmenting agents, anti-inflammatory agents, steroids, anti-acne agents, antioxidants, and advanced glycation end-product (AGE) inhibitors.
  • additional skin actives including but not limited to, botanicals, keratolytic agents, desquamating agents, keratinocyte proliferation enhancers, collagenase inhibitors, elastase inhibitors, depigmenting agents, anti-inflammatory agents, steroids, anti-acne agents, antioxidants, and advanced glycation end-product (AGE) inhibitors.
  • botanicals including but not limited to, botanicals, keratolytic agents, desquamating agents, keratinocyte proliferation enhancers, collagenase inhibitors, elastase inhibitors, depigmenting agents, anti-inflammatory agents,
  • composition may comprise additional active ingredients having anti-aging benefits, as it is contemplated that synergistic improvements may be obtained with such combinations.
  • exemplary anti-aging components include botanicals. Suitable botanical extracts include, without limitation, extracts from Abies pindrow, Acacia catechu, Anogeissus latifolia, Asmunda japonica, Azadirachta indica, Butea frondosa, Butea monosperma, Cedrus deodara, Emblica officinalis, Ficus benghalensis, Glycyrrhiza glabra, Ilex purpurea Hassk, Innula racemosa, Ligusticum chiangxiong, Ligusticum lucidum, Mallotus philippinensis, Mimusops elengi, Morinda citrifolia, Moringa oleifera, Naringi crenulata, Nerium indicum, Psoralea corylifolia, Stenol
  • anti-aging compounds include, without limitation, phytol,thiodipropionic acid (TDPA) and esters thereof; retinoids (e.g., retinol and esters thereof, such as retinol palmitate, retinol acetate and retinol propionate, and salts thereof, all-trans retinoic acid, 9-cis retinoic acid, phytanic acid and others); hydroxy acids (including alpha-hydroxyacids and beta-hydroxyacids), salicylic acid and salicylates; exfoliating agents (e.g., glycolic acid, 3,6,9-trioxaundecanedioic acid, etc.), estrogen synthetase stimulating compounds (e.g., caffeine and derivatives); compounds capable of inhibiting 5 alpha-reductase activity (e.g., linolenic acid, linoleic acid, finasteride, and mixtures thereof); barrier function enhancing agents (e.g.,
  • Further additional actives useful for topical application to skin include perilla oil, mangostine, palmitoyl lysylaminovaleroyl lysine (palmitoyl K-ava-K), palmatoyl tetrapeptide-10 (KTFK), L-4-thiazolylalanine, cis-6-nonenol, desthiobiotin, N-(4-mesyloxybenzyl)-N-methoxyethyl-4-chlorobenzene carboxamide, N-(4-mesyloxybenzyl)-N-isobutyl benzenesulfonamide, retinyl oleate, carvacrol, and mixtures thereof
  • the topical compositions of the present invention may also include one or more of the following: a skin penetration enhancer, an emollient, such as isopropyl myristate, petrolatum, silicones (e.g., methicone, dimethicone), oils, mineral oils, and fatty acid esters; a humectant, such as glycerin or caprylyl glycol, a skin plumper, such as palmitoyl oligopeptide, collagen, or collagen and/or glycosaminoglycan (GAG) enhancing agents, a sunscreen, such as avobenzone, an exfoliating agent, and an antioxidant.
  • a skin penetration enhancer such as isopropyl myristate, petrolatum, silicones (e.g., methicone, dimethicone), oils, mineral oils, and fatty acid esters
  • a humectant such as glycerin or caprylyl glycol
  • a skin plumper such
  • Suitable exfoliating agents include, for example, alpha-hydroxyacids, beta-hydroxyacids, oxa-acids, oxadiacids, and their derivatives such as esters, anhydrides and salts thereof.
  • Suitable hydroxy acids include, for example, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, 2-hydroxyalkanoic acid, mandelic acid, salicylic acid and derivatives thereof.
  • a preferred exfoliating agent is glycolic acid.
  • the exfoliating agent may comprise from about 0.1 wt % to about 80 wt % of the composition.
  • antioxidants examples include compounds having phenolic hydroxy functions, such as ascorbic acid and its derivatives/esters; beta-carotene; catechins; curcumin; ferulic acid derivatives (e.g. ethyl ferulate, sodium ferulate); gallic acid derivatives (e.g., propyl gallate); lycopene; reductic acid; rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherol and its derivatives; uric acid; or any mixtures thereof.
  • phenolic hydroxy functions such as ascorbic acid and its derivatives/esters; beta-carotene; catechins; curcumin; ferulic acid derivatives (e.g. ethyl ferulate, sodium ferulate); gallic acid derivatives (e.g., propyl gallate); lycopene; reductic acid; rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherol and
  • antioxidants are those that have one or more thiol functions (-SH), in either reduced or non-reduced form, such as glutathione, lipoic acid, thioglycolic acid, and other sulfhydryl compounds.
  • the antioxidant may be inorganic, such as bisulfites, metabisulfites, sulfites, or other inorganic salts and acids containing sulfur.
  • Compositions of the present invention may comprise an antioxidant preferably from about 0.001 wt % to about 10 wt%, and more preferably from about 0.01 wt% to about 5 wt%, of the total weight of the composition.
  • vitamins such as tocopherol and ascorbic acid
  • vitamin derivatives such as ascorbyl monopalmitate
  • thickeners such as hydroxyalkyl cellulose
  • gelling agents such as hydroxyalkyl cellulose
  • structuring agents metal chelating agents such as EDTA
  • pigments colorants, and pH adjusters.
  • compositions may optionally comprise other components known to those skilled in the art including, but not limited to, film formers, moisturizers, minerals, viscosity and/or rheology modifiers, anti-acne agents, insect repellents, skin cooling compounds, skin protectants, lubricants, fragrances, skin conditioners, hair conditioners, lakes, dyes, preservatives, or stabilizers, and mixtures thereof
  • film formers moisturizers, minerals, viscosity and/or rheology modifiers
  • anti-acne agents anti-acne agents
  • insect repellents skin cooling compounds
  • skin protectants lubricants
  • fragrances skin conditioners
  • hair conditioners lakes
  • dyes preservatives, or stabilizers
  • mixtures thereof and mixtures thereof
  • cosmetic compositions of the invention may contain any other compound for the treatment of skin disorders.
  • the composition may be formulated in a variety of product forms, such as, for example, an emulsion, lotion, cream, serum, spray, aerosol, cake, ointment, essence, gel, paste, patch, pencil, towelette, mask, stick, foam, elixir, concentrate, and the like, particularly for topical administration.
  • the composition is formulated as cream, an ointment, a gel, a serum, an emulsion, a spray, an aerosol, a patch, a mask, or a stick.
  • the invention provides a method for treating aging skin by topically applying a composition comprising a botanical extract, preferably in a cosmetically acceptable vehicle, over the affected area for a period of time sufficient to reduce, ameliorate, reverse or prevent dermatological signs of aging.
  • the improvement in the condition and/or aesthetic appearance is associated with the increase in collagen, procollagen, and elastin productions.
  • Specific improvements are selected from the group consisting of: reducing dermatological signs of chronological aging, photo-aging, hormonal aging, and/or actinic aging; preventing and/or reducing the appearance of lines and/or wrinkles; reducing the noticeability of facial lines and wrinkles, facial wrinkles on the cheeks, forehead, perpendicular wrinkles between the eyes, horizontal wrinkles above the eyes, and around the mouth, marionette lines, and particularly deep wrinkles or creases; improving the appearance of suborbital lines and/or periorbital lines; reducing the appearance of crow's feet; rejuvenating and/or revitalizing skin, particularly aging skin; reducing skin fragility; preventing and/or reversing of loss of glycosaminoglycans and/or collagen; ameliorating the effects of estrogen imbalance; preventing skin atrophy; preventing, reducing, and/or treating hyperpigmentation or hypopig
  • the composition will typically be applied to the skin one, two, or three times daily for as long as is necessary to achieve desired results.
  • the treatment regiment may comprise daily application for at least one week, at least two weeks, at least four weeks, at least eight weeks, or at least twelve weeks or more.
  • Chronic treatment regimens are also contemplated.
  • the effect of a composition on the formation or appearance of fine lines and wrinkles can be evaluated qualitatively, e.g., by visual inspection, or quantitatively, e.g., by microscopic or computer assisted measurements of wrinkle morphology (e.g., the number, depth, length, area, volume and/or width of wrinkles per unit area of skin).
  • the composition of the invention will be applied to the skin in an amount from about 0.001 to about 100 mg/cm 2 , more typically from about 0.01 to about 20 mg/cm 2 , and preferably about 0.1 to about 10 mg/cm 2 .
  • compositions of the invention will be useful for treating thin skin by topically applying the composition to thin skin of an individual in need thereof.
  • Thiin skin is intended to include skin that is thinned due to chronological aging, menopause, or photo-damage and skin that is thinning prematurely.
  • the treatment is for thin skin in men, whereas other embodiments treat thin skin in women, pre-menopausal or post-menopausal, as it is believed that skin thins differently with age in men and women, and in particular in women at different stages of life.
  • the method of the invention may be employed prophylactically to forestall aging including in individuals that have not manifested signs of skin aging, most commonly in individuals under 25 years of age.
  • the method may also reverse or treat signs of aging once manifested as is common in individuals over 25 years of age, or to slow the progression of dermatological aging in such individuals.
  • An Abrus fruticutosus extract was prepared as follows. A sample of 250g of dried material from the aerial portion of the plant was extracted with three portions of 1:1 ethanol/water (1335 ml, 800 ml, 700 ml) for a combined total of 2850 ml of extract. The ethanol was removed under vacuum, then sufficient additional water was added to achieve 1000 ml total volume. The resulting mixture was centrifuged at 8000 rpm for 10 minutes, then the supernatant was washed with three portions of dichloromethane (500 ml, 400 ml, 400 ml). The water phase was treated with 10 g of charcoal, filtered and then concentrated under vacuum to obtain 36.5 g of a solids. The same procedure was used to prepare the other extracts employed in Example 2.
  • Normal human dermal fibroblasts were cultured in 96-well tissue culture-treated plates, containing appropriate culture medium. Stock solutions of actives were made in an appropriate vehicle (water). Cells were treated with test material or respective vehicle control diluted in growth medium for 24 hours in a humidified 37°C incubator with 10% CO 2 . After incubation, growth medium from each plate was removed and 100 ⁇ L of lysis buffer was added to the wells and placed in 37°C incubator with 10% CO 2 for 30 minutes. At the end of incubation, the cells were collected in freezer plates and placed in -80°C freezer, until analysis.
  • Elastin Elastin
  • Collagen COL1A1
  • concentrations of each extract are provided based on the dry weight of the given plant extract, by which is meant the weight of the extract after volatile extraction solvents have been removed.
  • Table 2 Ingredient Name Elastin (ELN) Degree of upregulation (concentration of extract) Collagen (COL1A1) Degree of upregulation (concentration of extract) Justicia ventricosa +++ (0.1%) 0 (0.1, 0.01%) Archidendron clypearia ++ (0.1%) ++ (0.1%)
  • the cosmetic compositions set forth in Table 3 are illustrative of the invention and are useful for topical application to the skin to enhance its aesthetic appearance.
  • composition according to claim 10 may comprise the following further features, either in combination with any other composition claims, or separately:

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Claims (9)

  1. Verfahren zum Verbessern des ästhetischen Erscheinungsbildes von menschlicher Haut, umfassend topisches Auftragen einer wirksamen Menge eines Pflanzenextrakts in einem topisch unbedenklichen Vehikel auf einen Bereich der Haut, der dessen bedarf, wobei der Pflanzenextrakt ausgewählt ist aus der Gruppe, bestehend aus Justicia ventricosa, Archidendron clypearia und Kombinationen davon.
  2. Verfahren nach Anspruch 1, wobei die ästhetische Verbesserung der Haut ausgewählt ist aus der Gruppe, bestehend aus:
    (a) Behandlung, Verringerung und/oder Vorbeugung von feinen Linien oder Falten;
    (b)Verringerung der Hautporengröße;
    (c) Verbesserung der Dicke, Prallheit und/oder Straffheit der Haut;
    (d)Verbesserung der Glätte, Geschmeidigkeit und/oder Weichheit der Haut;
    (e)Verbesserung des Teints, der Leuchtkraft und/oder der Reinheit der Haut;
    (f) Verbesserung der Prokollagen- und/oder Kollagenproduktion;
    (g)Verbesserung der Erhaltung und Remodellierung von Elastin;
    (h)Verbesserung der Hautstruktur und/oder Förderung ihrer Erneuerung;
    (i) Verbesserung der Reparatur und/oder Funktion der Hautbarriere;
    (j) Verbesserung des Erscheinungsbilds von Hautkonturen;
    (k) Wiederherstellung des Glanzes und/oder der Strahlkraft der Haut;
    (l) Auffüllung von wichtigen Nährstoffen und/oder Bestandteilen in der Haut;
    (m) verringert durch Alterung und/oder Menopause;
    (n)Verbesserung der Feuchtigkeitsversorgung der Haut;
    (o)Erhöhung der Elastizität und/oder Spannkraft der Haut;
    (p)Behandlung, Verringerung und/oder Vorbeugung von Hauterschlaffung;
    (q)Verbesserung der Hautfestigkeit;
    (r) Verringerung von Pigmentflecken und/oder fleckiger Haut;
    (s) Verbesserung des Erscheinungsbilds von Aknenarben oder -spuren;
    (t) Verbesserung des Erscheinungsbilds von Dehnungsstreifen; und/oder
    (u)Verbesserung des Erscheinungsbilds von Cellulite.
  3. Verfahren nach Anspruch 2, wobei die ästhetische Verbesserung der Haut eine Behandlung, Verringerung und/oder Vorbeugung von feinen Linien und/oder Falten ist.
  4. Verfahren nach Anspruch 2, wobei die ästhetische Verbesserung der Haut eine Verbesserung der Dicke, Prallheit und/oder Straffheit ist.
  5. Verfahren nach Anspruch 2, wobei die ästhetische Verbesserung der Haut eine Erhöhung der Elastizität und/oder Spannkraft der Haut ist.
  6. Verfahren nach Anspruch 2, wobei die ästhetische Verbesserung der Haut eine Behandlung, Verringerung und/oder Vorbeugung von Hauterschlaffung ist.
  7. Verfahren nach Anspruch 2, wobei die ästhetische Verbesserung der Haut eine Verbesserung der Hautfestigkeit ist.
  8. Zusammensetzung, umfassend etwa 0,0001 Gew.-% bis etwa 90 Gew.-% eines Pflanzenextrakts, ausgewählt aus Justicia ventricosa, Archidendron clypearia oder Kombinationen davon, und ein topisch unbedenkliches Vehikel in Kombination mit einem oder mehreren Hautwirkstoffen, ausgewählt aus der Gruppe, bestehend aus Retinoiden, Antioxidanzien, α-Hydroxysäuren, Glykolsäure und Thiodipropionsäure und Estern davon.
  9. Zusammensetzung nach Anspruch 8, wobei die Zusammensetzung in Form einer Wasser-in-Öl- oder Öl-in-Wasser-Emulsion vorliegt.
EP12825830.8A 2011-08-24 2012-07-02 Zusammensetzungen zur kollagen- und elastinstimulierung sowie ihre verwendung Not-in-force EP2747573B1 (de)

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Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201422250A (zh) * 2012-12-11 2014-06-16 Avon Prod Inc Ｎｅｓｐｒｉｎ－２表現調節劑之用途及其組合物
TW201422246A (zh) * 2012-12-11 2014-06-16 Avon Prod Inc 藉由調節ｗｉｐｉ－１改善皮膚老化外觀之方法
CN105007985B (zh) 2013-03-07 2018-05-01 雅芳产品公司 用于处理受损毛发的组合物和方法
LU92277B1 (fr) 2013-09-11 2015-03-12 Joventis Sa Composé cosmétique
KR101747139B1 (ko) 2014-10-16 2017-06-14 동화약품주식회사 쥐꼬리망초 속 식물의 추출물 또는 분획물을 포함하는 조성물
PL3265053T3 (pl) 2015-03-05 2020-03-31 Avon Products, Inc. Sposoby leczenia skóry
US10076479B1 (en) 2018-05-08 2018-09-18 Avon Products, Inc. Methods for treating skin
CA3076249A1 (en) 2017-09-21 2019-03-28 The Brigham And Women's Hospital, Inc. Isolation, preservation, compositions and uses of extracts from justicia plants

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6146640A (en) 1998-08-31 2000-11-14 Dyke; John Paul Immune system catalyst
JP4280340B2 (ja) * 1998-10-28 2009-06-17 一丸ファルコス株式会社 保湿性植物抽出物を含有する化粧料組成物
DE19910704B4 (de) 1999-03-10 2006-04-20 Cognis Ip Management Gmbh Kosmetische Zubereitungen und deren Verwendung
JP4532706B2 (ja) 2000-09-08 2010-08-25 花王株式会社 化粧料
CA2439402A1 (en) 2001-03-02 2002-09-12 University Of Pittsburgh Of The Commonwealth System Of Higher Education Pcr method
WO2002100384A1 (en) 2001-06-12 2002-12-19 Hisamitsu Pharmaceutical Co., Inc. Sheet-like patch agent
US20030091665A1 (en) 2001-11-09 2003-05-15 Avon Products, Inc Topical cosmetic composition with skin rejuvenation benefits
US20030124205A1 (en) 2001-12-28 2003-07-03 Avon Products, Inc. Topical cosmetic composition having a natural plant active ingredient and method of using same
US6884783B2 (en) 2002-05-03 2005-04-26 Unigen Pharmaceuticals, Inc. 7-Hydroxy chromones as potent antioxidants
US7189419B2 (en) 2002-12-17 2007-03-13 Avon Products, Inc. Use of active extracts to lighten skin, lips, hair, and/or nails
US20050196450A1 (en) 2004-03-04 2005-09-08 Elka Touitou Method and composition for burned skin
CA2571642A1 (en) 2004-07-09 2006-02-16 University Of Pittsburgh - Of The Commonwealth System Of Higher Educatio N Identification of markers in lung and breast cancer
US20060024390A1 (en) 2004-07-27 2006-02-02 Alex Schauss Palm fiber-based dietary supplements
JP5041569B2 (ja) 2004-09-01 2012-10-03 丸善製薬株式会社 チロシナーゼ活性阻害剤、美白剤及び皮膚化粧料
US7618662B2 (en) 2004-12-22 2009-11-17 Avon Products, Inc Use of natural plant extracts in cosmetic compositions
US7514092B2 (en) 2004-12-22 2009-04-07 Avon Products, Inc. Compositions and methods of their use for improving the condition and appearance of skin
US8221766B2 (en) 2004-12-22 2012-07-17 Avon Products, Inc. Use of plant extracts to prevent and/or reduce the signs of subjective discomfort and/or irritation in the topical application of cosmetic products
CN100548321C (zh) 2004-12-29 2009-10-14 广州莱泰医药科技有限公司 猴耳环提取物用于制备抗过敏药物、食品及化妆品的应用
WO2007093839A1 (en) 2006-02-16 2007-08-23 Sederma New polypeptides kxk and their use
CN101099839A (zh) 2007-07-09 2008-01-09 汪朝田 一种外用中药药包及其使用方法
CN101129675B (zh) 2007-07-10 2010-11-17 郑学东 治疗风湿、类风湿的外用帖膏
CN101234153B (zh) 2007-12-27 2010-11-10 卢旭 治疗骨折的外用药物
JP2010090069A (ja) 2008-10-09 2010-04-22 Shiseido Co Ltd 美白剤および皮膚外用剤
FR2939316B1 (fr) 2008-12-05 2012-08-10 Limousine D Applic Biolog Ditesilab Soc Ind Utilisation cosmetique d'activateurs de l'autophagie des cellules cutanees.
US7993629B2 (en) 2008-12-23 2011-08-09 Avon Products, Inc. Topical compositions containing CIS-6-nonenol and its derivatives and methods for treating skin
US9901551B2 (en) 2009-04-20 2018-02-27 Ambra Bioscience Llc Chemosensory receptor ligand-based therapies
US8173184B2 (en) 2009-08-14 2012-05-08 Mary Kay Inc. Topical skin care formulations comprising botanical extracts
MX339842B (es) 2009-12-22 2016-06-14 Avon Prod Inc Composiciones estimuladoras de paxilina y usos cosmeticos de las mismas.
BR112012026875B1 (pt) 2010-06-11 2018-12-04 Avon Products, Inc. método cosmético para melhorar a aprência da pele afetada pela celulilte e para reduzir recorrência de celulite em uma área previamente afetada e kit
US8815265B2 (en) 2010-06-30 2014-08-26 Avon Products, Inc. Cosmetic use of N-substituted sulfonyloxybenzylamines and related compounds
EP2588593B1 (de) 2010-06-30 2017-08-23 Avon Products, Inc. Zusammensetzungen und verfahren zur magp-1-stimulation zur verbesserung des erscheinungsbildes der haut
US8771758B2 (en) 2010-06-30 2014-07-08 Avon Products, Inc. Use of Tiliacora triandra in cosmetics and compositions thereof
US8686013B2 (en) 2011-08-25 2014-04-01 Avon Products, Inc. Cosmetic use of substituted amino heterocylic carbamoyl analogs and related compounds
US9289365B2 (en) 2011-10-24 2016-03-22 Avon Products, Inc. Compositions and methods for stimulating collagen synthesis in the skin
HK1203842A1 (zh) 2011-12-13 2015-11-06 雅芳产品公司 杜茎山提取物及其使用方法
US8632827B2 (en) 2011-12-13 2014-01-21 Avon Products, Inc Modulation of thymosin beta-4 in skin
US9034396B2 (en) 2012-12-11 2015-05-19 Avon Products, Inc. Serissa japonica extracts and methods of use
US9186316B2 (en) 2012-12-11 2015-11-17 Avon Products, Inc. Stephanotis jasminoides extracts and methods of use
TW201422246A (zh) 2012-12-11 2014-06-16 Avon Prod Inc 藉由調節ｗｉｐｉ－１改善皮膚老化外觀之方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

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US10195136B2 (en) 2019-02-05
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EP2747573A1 (de) 2014-07-02

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